The reaction between peptide aldehydes and acylhydrazones affords derivatives that represent potential prodrugs for selective inhibition of lysosomal enzymes. BzPheal = Ala, obtained from the reaction between N-benzoyl-L-phenylalaninal and N-acetyl-L-alanine hydrazide, has been most carefully studied. When BzPheal = Ala is introduced into ongoing reactions catalyzed by alpha-chymotrypsin or papain, the rate of these reactions diminishes more rapidly with time than do those of controls lacking BzPheal = Ala. Furthermore, the disparity between run and control is much greater at pH 5 than at pH 7. The extent of inhibition (defined as explained in the text) at pH 5 can exceed that at pH 7 by 25-40-fold. The data are quantitatively explained by a reaction scheme that recognizes three important properties of BzPheal = Ala: (1) It undergoes hydrolysis at pH 5-7 to regenerate N-benzoyl-L-phenylalaninal; (2) the aldehyde thus liberated is a far more potent inhibitor for serine or cysteine proteases than is BzPheal = Ala; and (3) the rate constant for hydrolysis of BzPheal = Ala at pH 5 greatly exceeds that at pH 7.

中文翻译：

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蛋白水解酶的酸敏感潜伏抑制剂：合成和表征。

肽醛和酰基hydr之间的反应提供了衍生物，这些衍生物代表了选择性抑制溶酶体酶的潜在前药。从N-苯甲酰基-L-苯丙氨酸和N-乙酰基-L-丙氨酸酰肼之间的反应中获得的BzPheal = Ala，已得到最仔细的研究。当将BzPheal = Ala引入由α-胰凝乳蛋白酶或木瓜蛋白酶催化的正在进行的反应中时，这些反应的速率随时间的推移比没有BzPheal = Ala的对照的反应速度更快地降低。与在pH 7时相比，其抑制程度为5。在pH 5时，抑制程度（如本文所述）可以超过在pH 7时的抑制程度25-40倍。通过识别BzPheal = Ala的三个重要特性的反应方案对数据进行定量解释：（1）在pH 5-7下水解，再生出N-苯甲酰基-L-苯丙氨酸；（2）这样释放的醛比BzPheal = Ala对丝氨酸或半胱氨酸蛋白酶的抑制作用强得多。（3）pH 5时BzPheal = Ala的水解速率常数大大超过pH 7时的速率常数。